Ha ha. Drug Makers Required to Show Benefit

The highlighted sentence in the second paragraph of this article could have been taken from the Onion.
(This article reminds me of an old New Yorker cartoon that showed a doctor talking to a patient at his desk saying. "I'm going to give you a new medication that works almost as well as aspirin but costs a whole lot more.")

Austerity in Europe Puts Pressure on Drug Prices
By STEPHANIE NOVAK

PARIS —Profits at pharmaceutical companies have been declining or showing little growth for the last year as austerity measures across Europe lead to cuts in health care spending. Some analysts say this trend could continue until at least 2014.

Budget cuts mean that many European governments are not willing to pay as much for pills. But new laws in some countries are also putting pressure on companies to prove their drugs are effective or risk having them dropped from the coverage list, or covered at a lower rate...

(There are then many paragraphs boo hooing about how hard this will be on the poor Big Pharma companies.)

“2011 is the first year recorded where R.& D. is down in the industry as a whole,” Mr. Bergström said...

Adding to the challenge for companies is the need to show newly cost-conscious governments that their drugs are cost effective.

Germany, Europe’s largest pharmaceutical market, has required drug companies since January 2011 to prove the added benefit of a new medication by producing documentation comparing it with other treatments on the market...
Partly as a result of these changes, the German government reported saving 1.9 billion euros on drugs in 2011, three times the savings in 2010, Business Monitor International said.

Drug companies worry that actions in Germany could hurt sales in other European markets.

My snark is borne of the great lengths that acupuncture research studies have had to go to to show benefit. An incredibly high bar that few other aspects of medicine have had to reach. Info on my practice here.

Blockbuster Smoking Cessation Drug Linked to Heart Disease

I somehow missed the latest in a series of much-hyped, best-selling drugs turning out to have major problems. This article was released over the July 4th holiday, so I didn't notice it. Long story short, Chantix is still on the market and will be studied further. From the article one critic is quoted as saying, “It causes loss of consciousness, visual disturbances, suicides, violence, depression and worsening of diabetes. To this list we now can add serious cardiovascular events.” Wow, sounds bad. So why would they leave it on the market? Well maybe because it's "a product that has been prescribed to 13 million people and had $755 million in sales last year." Or this "Chantix is selling well overseas. In Japan, for instance, some pharmacies ran out for a while recently, even as the drug failed to meet expectations in the United States because of health warnings and bad publicity." Another fun fact was that physicians who prescribe the drug can expect to get one new cardiac event in every 28 patients taking the drug. But on the bright side, for every ten patients taking it, one will stop smoking (yes, one in ten) . So there's that.

July 4, 2011
Study Links Smoking Drug to Cardiovascular Problems
By DUFF WILSON

Chantix, the best-selling prescription drug for smoking cessation, was linked to an increased risk of a heart attack, stroke or other serious cardiovascular event for smokers without a history of heart disease compared with smokers who did not use the drug, according to a Canadian medical journal report released on Monday.

The finding added to previous warnings about the pill’s connection to psychiatric problems and cardiovascular risks for people with a history of heart disease...
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Unprecedented. Experts decry Medtronic Studies.

From the New York Times. A few of my other posts on conflicts of interest in corporate research here, here,and here.
Spine Experts Repudiate Medtronic Studies
By BARRY MEIER and DUFF WILSON

In an extraordinary move, a group of spine specialists are publicly repudiating the research of other experts that has backed the widespread use of a Medtronic bone growth product. In a series of reports published in a medical journal on Tuesday, the specialists called the research misleading and biased.
The repudiation, appearing in a full issue of The Spine Journal devoted to the topic, represents a watershed in the long-running debate over conflicts of interest for the sponsorship of scientific studies by makers of drugs and medical devices. It is extremely rare for researchers to publicly chastise colleagues, and editors of leading medical journals said they could not recall an instance in which a publication had dedicated an entire issue for such a singular purpose.

Medtronic, the nation’s biggest maker of medical devices, has been facing intensifying scrutiny over its promotion of Infuse, the bone growth product at the center of the controversy. The bioengineered material is used primarily in spinal fusions, a procedure in which spinal vertebrae are joined to reduce back pain.

Infuse is used in about a quarter of the estimated 432,000 spinal fusions performed in this country each year. The articles published on Tuesday charge that researchers with financial ties to Medtronic overstated Infuse’s benefits and vastly understated its risks by claiming there were none.

“It harms patients to have biased and corrupted research published,” five doctors wrote in a joint editorial that accompanied the reports. “It harms patients to have unaccountable special interests permeate medical research.”

“The spine care field is currently at a precarious intersection of professionalism, morality and public safety,” Dr. Christopher M. Bono, editor of the special edition, said in a statement. “As physicians and journal editors, we felt an obligation to present a thorough examination of this controversial issue.”

It is too early to predict how the articles will affect the financial fortunes of Medtronic, which earned an estimated $900 million from Infuse in its most recent fiscal year. ..


Medtronic officials acknowledged in interviews that it was common for them to review studies of its products before publication. However, they sought to distance themselves from the content of the published reports, and said outside researchers, not the company, had determined the significance of data and how it should be presented. At the heart of the issue are potential side effects related to Infuse’s use that emerged during patient studies conducted about a decade ago by outside researchers with significant financial ties to Medtronic.

Medtronic, as required, reported that data to the F.D.A., and the agency considered the rate of those complications significant enough in some cases to require the company to list them on Infuse’s label. But in reporting on such studies in 13 medical journal articles published during the last decade, researchers whose studies were paid for by Medtronic maintained that Infuse’s use was not tied to any complications.
In one article released Tuesday, experts said those reports played down Infuse’s risks and slanted them to favor Infuse’s performance over a bone graft, the material traditionally used in a fusion. Those experts estimated that the incidence of adverse events in connection with Infuse’s use ranged from 10 to 50 percent, depending on how it was used.

Those side effects, they said, include male sterility, infection, bone loss and unwanted bone growth. A stronger version of Infuse, called Amplify, was recently rejected for approval by the F.D.A. because of concerns about possible cancer risks.

In 2008, the agency warned the public that it had received reports of life-threatening injuries associated with the use of Infuse in the cervical portion of the spine, a use that was not approved by the agency.

Dr. Eugene J. Carragee, editor of The Spine Journal, said he believed that Infuse was a valuable product for patients who were not candidates for a bone graft. But he added that the publication had undertaken the review because he and other experts hoped to cleanse the scientific record.

While Dr. Carragee said some researchers involved in the earlier reports were not influenced by links to Medtronic, he found it difficult to give those with major financial ties to the company such a pass. The median amount of Medtronic money received over time by researchers involved in some studies ranged from $12 million to $16 million, with most of that going to a few individuals, The Spine Journal estimated.
“A consistent number of people involved with these studies got extraordinary sums,” he said.

Tuesday’s articles added to an expanding number of studies pointing to serious side effects suffered by patients given Infuse. The journal also published an editorial by Dr. Charles L. Branch Jr., a Medtronic consultant, who said that the growing controversy over Infuse reflected a need to develop better ways to monitor and examine the off-label uses of medical products.

Infuse “appears to have been assigned the role of the poster child for all that is wrong with ‘off-label’ or physician-directed use of a novel beneficial technology,” wrote Dr. Branch, a neurosurgeon at the Wake Forest Baptist Medical Center in Winston-Salem, N.C.

Several researchers who were involved in the Medtronic-sponsored studies have defended their reports as scientifically sound and free of company influence, either directly or indirectly.

For example, one of them, Dr. Thomas A. Zdeblick of the University of Wisconsin, said that he did not have a “direct financial interest in the success of Infuse or Medtronic.” Over the years, Dr. Zdeblick has received over $20 million in royalty payments from Medtronic in connection with patents on devices, including one that is used with Infuse...

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Ghost writing Medical Research and Its Repercussions, from the Atlantic

Playing Doctor

How to spin pharmaceutical research
By Carl Elliott

This is another article about the corruption of medical research, but this one focuses on a more subtle aspect of industry sponsored research: the ghost writer. It has an amusing intro where we meet a ghost writer, Dave, and how he is taught to "spin" research findings to highlight the beneficial aspects of a given drug. You should really read the whole article, it's not too long.

The mechanics of the ghostwriter’s job are fairly simple, David says. Early on, a medical-communications agency and its pharmaceutical-company sponsors will agree on a title for an article and a potential author, usually an academic physician with a reputation as a “thought leader.” The agency will ask the thought leader to “author” the article, sometimes in exchange for a fee. The ghostwriter will write the article, or perhaps an extended outline containing the message the company wants to transmit, and send it along to the physician, who may make some changes or simply sign it as written and submit it to a journal, usually scrubbed of any mention of the ghostwriter, the agency, or the pharmaceutical company. David says he rarely even sees the published articles he writes.

Every so often, the issue of ghostwriting moves out of medical schools, where it is generally tolerated or ignored, and into the wider public sphere, where it is treated as a moral scandal. The most recent burst of outrage came in July during an investigation by the U.S. Senate Finance Committee, which has been looking into whether GlaxoSmithKline tried to steer attention away from the cardiac risks of its diabetes drug Avandia (whose use was recently restricted by the Food and Drug Administration). The committee found not merely that GSK had “downplayed scientific findings” to minimize the apparent risks of Avandia, but that it had used a ghostwriting campaign for the drug. (The company had called the ghosting effort “Case Study Publication for Peer Review,” or CASPPER.)

Ghostwritten articles surface again and again in litigation (in cases concerning Vioxx, Fen-Phen, Zyprexa, Premarin, Neurontin, and Zoloft, to mention just a few). Years before the Avandia scandal, GlaxoSmithKline paid $2.5 million to the State of New York to settle a lawsuit alleging that it had concealed studies suggesting an increased risk of suicidal behavior in children and teenagers taking Paxil, most notoriously in an article “authored” by Dr. Martin Keller of Brown University. One 2003 study in The British Journal of Psychiatry found that ghostwriters working for a single medical-communications agency had produced more than half of all medical-journal articles published on Zoloft over a three-year period.

It goes on to say that the moral outrage is often about "plagiarism," when the real crime, as David puts it, is that "spinning the data perverts science." Depressingly enough, it looks as though it is not going to stop any time soon. The journals have some weak rules about acknowledging some "editorial assistance," but allow the practice to continue. As an example, the Paxil article as noted above, has not been retracted in any way, so probably goes on being cited by unwitting practitioners. The ghost writers are well paid, but just tools to the greater enterprise of the pharmaceutical sales, and are not the real problem. As it says in the article " Medical writing has little glamour, and whatever moral purpose it might once have carried has been rubbed away by the constant friction with commerce." So for scientists by training, like Dave, this work can be quite demoralizing. Unfortunately, the whole set up is also quite dangerous.

Here are some previous posts dealing with the similar issues. Here, here, here, and here.

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Drugs causing the problems they're supposed to prevent

From the NYTimes:

"In the past month, the Food and Drug Administration has concluded that in some cases two types of drugs that were supposed to be preventing serious medical problems were, in fact, causing them.
One is bisphosphonates, which is widely used to prevent the fractures, especially of the hip and spine, that are common in people with osteoporosis. Those drugs, like Fosamax, Actonel and Boniva, will now have to carry labels saying they can lead to rare fractures of the thigh bone, a surprising new discovery that came after another surprise — that they can cause a rare degeneration of the jawbone.
The other is Avandia, which is widely prescribed for diabetics, whose disease puts them at risk for heart attacks and heart failure. Two-thirds of diabetics die of heart problems, and a main reason for taking drugs like Avandia is to protect them from that..."

They then go on to quote experts who feel that the FDA doesn't do enough to track drugs after they've been turned loose on the (unsuspecting) public. Since drugs only undergo a relatively short testing period, it would, of course make sense to continue tracking drugs once on the market. Where that money will come from I have no idea in this political climate, especially since the FDA has shown to be infiltrated with people from the drug industry with a vested interest. (See blog post "When oversight means overlook")
Given the shortcomings, and lack of oversight in the FDA I think it makes utmost sense as a health care consumer to wait at least 7 years before taking any newly released drug. Let others be the guinea pigs and if possible, take the version of any medication that is tried and true if given a choice. It's often cheaper, too.
I like to think that attitudes are changing among physicians, and that they're less willing to prescribe newly minted drugs, but I'm not sure if there is any evidence for that. I understand the drug companies rushing drugs to market, after all there is a boat load of money to be made. But I'm not sure I understand the eagerness of physicians to enable them. It could be pressure from patients themselves, who knows. But they should remind themselves of their oath to "first do no harm" and consider counseling weight bearing exercise and dietary changes before bisphonphonates and Avandia.

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Doctor Groups Urge End to Corporate Ties to Research

An article in the JAMA (Journal of the American Medical Association) published yesterday, April 1, was widely reported on the radio and today in the NYTimes and other publications http://www.nytimes.com/2009/04/02/health/policy/02journal.html?_r=1&ref=health.
A group of physicians and physicians groups are advocating for the elimination of funding by pharmaceutical companies for medical research because of the flagrant conflicts of interest. The concern is that these restrictions "were essential if physician associations are to maintain their scientific integrity and the trust of their patients."

This trust is clearly eroding. I see more evidence of this every day in my practice.

More discussion at a previous blogpost http://ksparrowmd.blogspot.com/2009/04/corruption-between-drug-companies-and.html

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Care Instead of Pills for Alzheimer's

This opinion piece in the LATimes by Ira Rosofsky March 19, 2009 crystallizes an argument that I would love to see have more mainstream traction. The argument is to weigh the cost of some of these new "wonder drugs" against how that money could be better spent in other types of care. This argument could be applied to a number of other conditions besides Alzheimer's dementia. I've been seeing a recent push to medicate "pre-diabetic" patients. Seen as representing a huge target population ($$$) Big Pharma is rushing to find a way to get drugs to these patients. Hey, here's an idea: why not put that money toward available, fresh produce. Where diabetes is most prevalent is often in the poorest areas of the country where access to fresh food is scarce.
Ira Rosofsky is a psychiatric nurse taking care of elderly patients. He sees them being medicated with expensive dementia drugs with a very dubious record of effectiveness. He also sees them being medicated with psychoactive drugs (anti-depressives, anti-psychotics) often just for being "ornery." Even ignoring ever-present problem of side effects- especially in the elderly- the costs of these drugs is extremely high to the end consumer. If one takes into account the enormous marketing budgets in addition, these dementia medications represent a huge amount of money. This author makes the case very succinctly:
"But why not admit the failure of medication and instead spend some of those billions of dollars on more staff to hold the hands of both patients and their families? Beyond nurturance, much of the savings from giving up on cost-ineffective medications could be diverted to basic research that might yield not only statistically significant but meaningful and large improvements -- even a cure."

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